Antibodies are effector proteins in the adaptive immune system. Each antibody is made up of a heterodimeric complex consisting of two linked heavy chains, and each individual heavy chain is linked to an identical light chain. At the end of the heavy and light chains is a variable region that, when in complex, combines to form the “paratope” of the antibody. The paratope is the section of the antibody that gives specificity to binding, allowing each different antibody to recognize a unique “epitope” which is a structure presented by an antigen. The adaptive immune systems of jawed vertebrates are capable of generating a large diversity of possible antibodies—in theory being ˜1014 for humans.
The diversity of antibodies is created by two processes: 1) the process of gene recombination and 2) the process of somatic hypermutation and affinity maturation. Gene recombination occurs during B cell development and results in a seemingly random combination of several regions of the genome (e.g., VDJ recombination in heavy chains) to create a functional antibody sequence. In addition to the combinatorial diversity of gene usage, this process also results in non-templated base additions or deletions at the junctions. The same process happens in the light chains to create a unique light chain. In some species, including rabbits and chickens, antibody diversity is also generated through a process of gene conversion.
Within each mature B cell, a unique heavy and light chain come together to create a unique antibody sequence that is displayed as a receptor (BCR) on the surface of the B cell. After challenge by a foreign antigen, if a BCR binds to the antigen (and also receives appropriate signals from T cells) the B cell divides and expands. During this division somatic mutation occurs within the genes encoding antibody variable regions. If the mutation improves binding to the antigen, the B cell continues to divide and obtains a selective advantage, whereas if the mutation destroys binding, the cell ultimately dies. As a result, each mature B cell that recognizes a given antigen gives rise to a diversity of different, but closely related, antibodies that have optimized binding properties.
T cell receptors (TCRs), displayed on mature T cells, are created by a similar process of gene recombination with the following differences: (i) TCRs are formed by a simple dimer complex (for example consisting of an alpha and a beta chain), (ii) TCRs do not undergo somatic hypermutation or affinity maturation, (iii) TCRs do not recognize native antigens but rather MHC-peptide complexes displayed by cells, and (iv) TCR formation is subject to stricter regulation to ensure recognition of MHC and to avoid auto-reactivity (the latter also happens with BCRs but to a lesser extent).